Trial Outcomes & Findings for A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRAVO) (NCT NCT00486018)

Last Updated: 2017-05-10

Results Overview

BCVA score in the study eye was based on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

397 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2017-05-10

Participant Flow

Please note that although the table below is titled "Overall Study," the completion rates are for the 6-month Treatment Period only (i.e., does not include the 6-month Observation Period data).

Participant milestones

Participant milestones
Measure	Sham Injection Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Overall Study STARTED	132	134	131
Overall Study Received Drug (Safety Population)	131	134	130
Overall Study COMPLETED	123	128	125
Overall Study NOT COMPLETED	9	6	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRAVO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Injection n=132 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=131 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Total n=397 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 12.7 • n=5 Participants	66.6 years STANDARD_DEVIATION 11.2 • n=7 Participants	67.5 years STANDARD_DEVIATION 11.8 • n=5 Participants	66.4 years STANDARD_DEVIATION 11.9 • n=4 Participants
Age, Customized < 45 years	8 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	17 participants n=4 Participants
Age, Customized 45 to < 65 years	59 participants n=5 Participants	51 participants n=7 Participants	51 participants n=5 Participants	161 participants n=4 Participants
Age, Customized 65 to < 85 years	60 participants n=5 Participants	74 participants n=7 Participants	69 participants n=5 Participants	203 participants n=4 Participants
Age, Customized ≥ 85 years	5 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants	16 participants n=4 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	67 Participants n=7 Participants	60 Participants n=5 Participants	185 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	67 Participants n=7 Participants	71 Participants n=5 Participants	212 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the last-observation-carried-forward (LOCF) method.

BCVA score in the study eye was based on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Outcome measures

Outcome measures
Measure	Sham Injection n=132 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=131 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months Baseline	54.7 Units on a scale Standard Deviation 12.2	56.0 Units on a scale Standard Deviation 12.1	53.0 Units on a scale Standard Deviation 12.5
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months Change from Baseline at Month 6	7.3 Units on a scale Standard Deviation 13.0	16.6 Units on a scale Standard Deviation 11.0	18.3 Units on a scale Standard Deviation 13.2

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

BCVA score based on the ETDRS visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Outcome measures

Outcome measures
Measure	Sham Injection n=132 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=131 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Percentage of Participants Who Gained ≥ 15 Letters in BCVA Score at Month 6 Compared With Baseline	28.8 Percentage of participants Interval 21.1 to 36.5	55.2 Percentage of participants Interval 46.8 to 63.6	61.1 Percentage of participants Interval 52.7 to 69.4

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

BCVA score based on the ETDRS visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters. The percentage of subjects who lost \<15 letters will be greater than the percentage of subjects who "gained \>=15 letters" as "losing \<15 letters" includes both those who gained \>=15 letters and those who were "stable" (i.e. lost between 1 and 14 letters, had no change, or gained between 1 and 14 letters).

Outcome measures

Outcome measures
Measure	Sham Injection n=132 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=131 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Percentage of Participants Who Lost < 15 Letters in BCVA Score at Month 6 Compared With Baseline	95.5 Percentage of participants Interval 90.5 to 98.0	100 Percentage of participants Interval 97.4 to 100.0	98.5 Percentage of participants Interval 94.6 to 99.7

SECONDARY outcome

Timeframe: 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

A central reading center assessed all optical coherence tomography (OCT) images. Central foveal thickness was defined as the center point thickness.

Outcome measures

Outcome measures
Measure	Sham Injection n=132 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=131 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Percentage of Participants With a Central Foveal Thickness of ≤ 250 μm at Month 6	45.5 Percentage of participants Interval 37.0 to 53.9	91.0 Percentage of participants Interval 86.2 to 95.9	84.7 Percentage of participants Interval 78.6 to 90.9

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

A central reading center assessed all OCT images. Central foveal thickness was defined as the center point thickness.

Outcome measures

Outcome measures
Measure	Sham Injection n=132 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=131 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Absolute Change From Baseline in Central Foveal Thickness at Month 6 Mean Absolute Change from Baseline at Month 6	-157.7 μm Standard Deviation 224.2	-337.3 μm Standard Deviation 224.4	-345.2 μm Standard Deviation 238.2
Mean Absolute Change From Baseline in Central Foveal Thickness at Month 6 Baseline	488.0 μm Standard Deviation 192.2	522.1 μm Standard Deviation 201.9	551.7 μm Standard Deviation 223.5

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population; however, patients without a baseline score were excluded from analysis.

The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A3, A4, and A5 pertained to the Near Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.

Outcome measures

Outcome measures
Measure	Sham Injection n=129 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=133 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Near Activities Subscale Score at Month 6 Baseline	69.6 Points on the NEI VFQ-25 subscale Standard Deviation 20.2	67.9 Points on the NEI VFQ-25 subscale Standard Deviation 22.1	69.4 Points on the NEI VFQ-25 subscale Standard Deviation 20.5
Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Near Activities Subscale Score at Month 6 Change from baseline at Month 6	7.3 Points on the NEI VFQ-25 subscale Standard Deviation 15.3	12.1 Points on the NEI VFQ-25 subscale Standard Deviation 17.3	13.7 Points on the NEI VFQ-25 subscale Standard Deviation 18.0

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population; however, patients without a baseline score were excluded from analysis.

The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A6, A7, and A8 pertained to the Distance Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.

Outcome measures

Outcome measures
Measure	Sham Injection n=129 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=133 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Change From Baseline in the NEI VFQ-25 Distance Activities Subscale Score at Month 6 Mean Change from Baseline at Month 6	6.3 Points on the NEI-VFQ-25 subscale Standard Deviation 15.0	10.3 Points on the NEI-VFQ-25 subscale Standard Deviation 17.2	11.3 Points on the NEI-VFQ-25 subscale Standard Deviation 16.6
Mean Change From Baseline in the NEI VFQ-25 Distance Activities Subscale Score at Month 6 Baseline	76.4 Points on the NEI-VFQ-25 subscale Standard Deviation 20.6	76.0 Points on the NEI-VFQ-25 subscale Standard Deviation 20.5	76.7 Points on the NEI-VFQ-25 subscale Standard Deviation 18.1

Adverse Events

Sham Injection

Serious events: 6 serious events

Other events: 115 other events

Deaths: 0 deaths

Ranibizumab Injection 0.3 mg

Serious events: 14 serious events

Other events: 125 other events

Deaths: 0 deaths

Ranibizumab Injection 0.5 mg

Serious events: 14 serious events

Other events: 115 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Sham Injection n=131 participants at risk Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 participants at risk Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 participants at risk Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Angina Unstable	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Bradycardia	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Ear and labyrinth disorders Vertigo	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Glaucoma	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Gaze Palsy	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Visual Acuity Reduced	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Ischemia	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Neovascularization	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Vein Occlusion	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Detachment	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Tear	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Macular Edema	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Colonic Polyp	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Intra-Abdominal Hematoma	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Rectal Hemorrhage	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Hepatobiliary disorders Cholecystitis	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Cellulitis	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Osteomyelitis	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Endophthalmitis	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Lobar Pneumonia	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Pneumonia	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.5% 2/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Sinusitis	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Urinary Tract Infection	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Gastroenteritis Viral	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Injury, poisoning and procedural complications Corneal Abrasion	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Injury, poisoning and procedural complications Post Procedural Hemorrhage	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Injury, poisoning and procedural complications Pelvic Fracture	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Metabolism and nutrition disorders Dehydration	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.75% 1/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Nervous system disorders Cerebral Hemorrhage	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Nervous system disorders Thalamus Hemorrhage	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.76% 1/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.77% 1/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Vascular disorders Hypertension	0.00% 0/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.5% 2/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.

Other adverse events
Measure	Sham Injection n=131 participants at risk Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=134 participants at risk Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 participants at risk Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Eye disorders Conjunctival Hemorrhage	42.0% 55/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	59.7% 80/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	54.6% 71/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Eye Irritation	7.6% 10/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.0% 8/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.2% 8/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Eye Pain	14.5% 19/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	24.6% 33/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	16.2% 21/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Foreign Body Sensation in Eyes	6.1% 8/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	4.5% 6/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.9% 9/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Maculopathy	8.4% 11/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	11.9% 16/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	12.3% 16/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Myodesopsia	1.5% 2/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	12.7% 17/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	4.6% 6/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Ocular Hyperemia	4.6% 6/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	9.7% 13/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.2% 8/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Ocular Vascular Disorder	12.2% 16/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	15.7% 21/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.7% 10/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Depigmentation	4.6% 6/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	4.5% 6/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	11.5% 15/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Exudates	15.3% 20/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	27.6% 37/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	24.6% 32/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Hemorrhage	13.7% 18/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	17.2% 23/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	17.7% 23/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Vascular Disorder	6.9% 9/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.5% 10/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	11.5% 15/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Vision Blurred	3.8% 5/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.7% 5/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.2% 8/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Vitreous Detachment	2.3% 3/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.0% 8/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.8% 5/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Nasopharyngitis	5.3% 7/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	4.5% 6/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.4% 7/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Sinusitis	3.1% 4/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.5% 10/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.8% 5/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Investigations Intraocular Pressure Increased	2.3% 3/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.2% 7/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.9% 9/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Nervous system disorders Dizziness	5.3% 7/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.7% 5/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Nervous system disorders Headache	4.6% 6/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.7% 9/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	2.3% 3/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Vascular disorders Hypertension	9.2% 12/131 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	8.2% 11/134 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.7% 10/130 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.